Title : Mechanisms Of sars-cov-2 neurovirulence in chemosensory dysfunction and prognosis of affected patients: Systematic review
Abstract:
Introduction: Severe acute respiratory syndrome coronavirus-2 virus (SARS-COV-2) was officially identified on January 2020 following investigations of pneumonia cases of unknown origin. Clinical presentation presents variations in symptom duration, severity, and complications. Among the most frequent symptomatic manifestations are chemosensory dysfunctions such as anosmia and ageusia. Also, it may influence an individual's nutrition and culminate in disorientation and social withdrawal. Therefore, the scope of this review is to identify the neurovirulence mechanisms related to chemosensory dysfunction presented by SARS-COV-2 and to evaluate how the remission of olfactory symptoms and their prognosis develop in COVID-19 patients.
Methods: A systematic review of the literature was made, using databases such as PUBMED, VHL, MEDLINE, LILACS, and ScienceDirect. The keywords were consulted on DECS/MESH: (COVID-19 or SARS-COV-2) AND (ANOSMIA OR AGEUSIA) AND (MECHANISM OR DISORDER).
Results: They were elucidated according to the PRISMA methodology. In addition to the flow chart, a table was developed with all the articles included in this review, their respective objectives, study methodology, samples, and results. 13 articles were included.
Discussion: The pathogenesis of SARS-COV-2-related chemosensory dysfunctions includes the destruction of the olfactory receptor neurons (ORNs). The damage results from the action of toxic inflammatory factors, due to an inflammatory storm, such as TNF-α, interleukin-1B (IL-1B), IL-6 and infiltrating inflammatory cells. Recent histopathological studies showed findings such as leukocyte infiltration in the lamina propria, focal atrophy of the olfactory mucosa, and neuronal fibres in the acute phase of infection. When analysing a patient with persistent anosmia, a massive disruption of the olfactory epithelium and mild chronic inflammatory infiltrate were found. Studies point out that IL-6 acts as an endogenous substance that regulates the olfactory neuronal activity and directly inhibits olfactory function. Both the peripheral and central actions of IL-6 contribute to the pathogenesis of anosmia and ageusia. Peripheral IL-6 acts on the levels of infected cell receptors. Central IL-6 acts at the level of the intermediate taste and smell pathways, especially in the thalamus. The taste (ventral posteromedial nucleus) and smell (dorsomedial nucleus) pathways converge. These nuclei are located close to the hypothalamus, which houses the thermoregulatory centre, an important target of IL-6. In a sample of 67 patients diagnosed with COVID-19, 65.7% reported olfactory dysfunction alone and 8.95% reported an association between olfactory and taste dysfunction. Most patients restore smell perception within 1–2 weeks, likely due to the differentiation of progenitor cells into mature ORNs. However, opposing arguments state that this period is too short to achieve complete neuronal regeneration. A prospective randomised multicentre study demonstrated the effectiveness and speed of olfactory function recovery with corticosteroids therapy in patients with long-term severe olfactory disturbances post-COVID.
Conclusion: Thus, the mechanisms of neurovirulence of SARS-COV-2 involves ACE-2 activity and injury to the olfactory bulb are triggered by the inflammatory cascade with the action of pro-inflammatory cytokines. The prognosis of COVID-19 infection is directly related to the patient's comorbidities but tends to be better in patients who present with anosmia and ageusia early. Female patients were more affected.
